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Biomedical subjects

W Becker

Publications and source records attributed to W Becker.

At least 235 records · Page 13Linked to original sources
PubMed1996

Detection thresholds for object motion and self-motion during vestibular and visuo-oculomotor stimulation.

We compared the detection threshold for object motion with that of self-motion in space in healthy human subjects. Stimuli consisted of horizontal rotations of subjects' body with a fixation spot kept in fixed alignment with their heads (vestibular stimulus), rotation of the fixation spot relative to the stationary subjects (visuo-oculomotor stimulus), and a combination thereof by applying rotations of subjects body relative to the stationary object (sinusoidal oscillations, 0.025-0.4 Hz). Two series of experiments were performed. 1) One group of subjects was instructed to attend to, and to indicate the occurrence of, either object or self-motion. 2) A second group was instructed not only to detect the occurrence of a perception, but also to quality it either as object motion or self-motion, depending on which modality dominated perceptually. With either instruction it was found that all three stimulus conditions could evoke both, either an object motion perception or a self-motion perception. The detection thresholds of both perceptions were essentially similar. Thresholds were highest with the vestibular stimulus, intermediate with the stimulus combination, and lowest with the visuo-oculomotor stimulus. The vestibular threshold depended on stimulus frequency, in that it decreased with increasing frequency. Thereby, it became similar to the visuo-oculomotor one, which was essentially constant across frequency. Probability of occurrence of the perceptions in the first experimental series was considerably higher than in the second series, suggesting an important role of attentional mechanisms. In the second series, percent frequency of occurrence of veridical perception (object motion with visuo-oculomotor stimulus, self-motion with stimulus combination) was at chance level (50%) at low stimulus frequency, but was augmented considerably at high frequency. We assume that the latter effect is brought about by a visual-vestibular conflict measure by which the visual stimulus (light spot) is qualified as representing either a moving object or a spatial reference for self-motion. While at suprathreshold stimulus intensities the conflict can determine perception magnitude, at threshold levels its influence is restricted mainly on the probability of occurrence of object and self-motion perception.

Adult↗
PubMed1996

Is perceived angular displacement the time integral of perceived angular velocity?

Estimates of rotational self-displacement and self-velocity have been used interchangeably in vestibular psycho-physics to characterize vestibular ego-motion perception. However, the assumption underlying this indiscriminate use has never been tested. The assumption holds that the two estimates are equivalent, with the displacement estimates reflecting the time integral of the signal underlying the velocity estimate. We tested this hypothesis by directly comparing displacement and velocity estimates. Two groups of healthy young subjects (2 x n = 15) were presented with the same vestibular stimuli (horizontal whole body rotations in the dark in the form of velocity steps of 5, 10, 20, and 40 degrees/s with 1, 2, 4, 8, and 16 s duration, yielding position ramps of 5, 10, 20, 40, 80, 160, and 320 degrees total displacement). The first subject group estimated peak velocity, and the second group estimated total displacement, both groups using a comparable psychophysical procedure (Stevens' magnitude estimation). The experimentally obtained velocity estimates were used to predict the displacement estimates. To this end, the velocity signal was assumed to decay exponentially from the reported peak value (reflecting the dynamics of peripheral and early central vestibular mechanisms) and was mathematically integrated. Predicted and measured displacement estimates were similar when a time constant of 20 s was assumed, which is in good agreement with earlier studies. We conclude that vestibular displacement estimates can, indeed, be considered equivalent to vestibular velocity estimates, at least for the stimulus parameters used.

Adult↗
PubMed1996

The effects of extracts from Tetrapleura tetraptera (Taub.) and Bayluscide on cells and tissue structures of Biomphalaria glabrata (Say).

Subchronic experiments were conducted with low concentrations of saponins from Tetrapleura tetraptera and Bayluscide to study the ultrastructural effects of these molluscicides on Biomphalaria glabrata. The ratio of the digestive cells to the crypt cells was inverted in molluscicide treated snails which showed an increase in the number of secretory cells and a decrease in the number of digestive cells. In the snail foot connective tissues, dose-dependent autolytic areas were observed. The major ultrastructural effects were seen in the digestive gland with dose-dependent autolysis of the membranous structures such as the golgi apparatus, mitochondria and endoplasmic reticulum. The results show that the molluscicides produced non-specific effects on the membranous structures.

Animals↗
PubMed1996

A pilot study comparing screw-shaped implants. Surface analysis and histologic evaluation of bone healing.

The purpose of this study was to compare surface treatment and bone formation adjacent to 2 screw shaped implants of similar design manufactured by two different companies. The test implants were manufactured by SERF (Decines, France), while the controls were manufactured by Nobelpharma (Goteborg, Sweden). The surface of 3 standard 3.75 mm test and 3 standard 3.75 mm control implants were investigated by means of scanning electron microscopy (SEM), X-ray micro-analysis, electron spectroscopy for chemical analysis (ESCA) and surface topography analysis. There was a microscopic difference on the thread design (SEM). Test threads were flat at the edge, while controls appeared rounded at the edge of the threads. Tests and controls were made of commercially pure titanium, with a regular topography. Results of ESCA indicated that the carbon peak for SERF implants was slightly higher than for the Brånemark implants. 5 test and 5 control implants were installed into the epiphyseal head of the femur of 2 ewes using a standardized surgical technique. In order to stain the bone for histologic analysis, oxytetracycline injections were given 17 and 8 days before the animals were sacrificed. The animals were sacrificed 12 weeks after implant placement. Histomorphometric analysis indicated that there was an average bone to implant contact orf 68% for the test implants and 61% for the controls. There were no statistical differences between tests and controls. The preliminary results of this pilot study indicated that early bone healing for the 2 screw shaped implants investigated were similar.

Animals↗
PubMed1996

Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell ALL.

Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission. Similarly, in SCID mice with advanced disease a significant prolongation of survival was seen. The therapeutic effects were dependent upon dose and affinity of the antibody. TH-69 is a high-affinity antibody (7.6 x 10(9) M-1) that rapidly induced modulation during treatment. The Fc-portion of the antibody was required for effective tumour cell killing. Complement deposition was found on tumour sections after TH-69 treatment and in part may account for tumour destruction. There was no evidence for antibody-dependent cellular cytotoxicity (ADCC). The kinetics of tumour disappearance suggested the initiation of a programmed cell death (PCD), despite the lack of significant DNA fragmentation. Unmodified high-affinity antibodies to the T-cell antigen CD7 have potential for T-cell ALL therapy.

Animals↗
PubMed1996

Evidence that reduced leptin levels, but not an aberrant sequence of leptin or its receptor, contribute to the obesity syndrome in NON mice.

NON mice exhibit a polygenic syndrome of mild obesity which is less pronounced than that of the ob and db strains. Here, we have shown that the syndrome is accompanied by a rise in leptin mRNA levels in adipose tissue, corresponding with the increase in adipose tissue mass. Surprisingly, levels of the leptin protein in adipose tissue and serum were comparable to those of lean control animals (BL57/Ksj-+/+), and markedly lower than those in db/db-mice. The coding regions of the cDNA sequences of both leptin and the leptin receptor from NON mice were identical with those of the wild-type sequences. We suggested that low levels of leptin in adipose tissue and serum contribute to the obesity of NON mice.

Adipose Tissue↗
PubMed1996

Rapid imaging of infections with a monoclonal antibody fragment (LeukoScan).

The diagnostic accuracy for imaging infection with a technetium-99m-labeled antigranulocyte Fab' fragment (LeukoScan) was prospectively examined in a multicenter study. Scintigraphy was performed in 53 patients at 1 to 6 hours and at 24 hours after injection of the labeled antibody fragment. Thirty-nine sites of infection were detected and confirmed by histologic study, cytologic study, other imaging procedures, or by followup. Thirty-eight of the 53 patients also were studied with technetium-99m-Exametazim or indium-111-oxine labeled leukocytes within 1 week of the LeukoScan study. In 21 patients with 25 osteomyelitic lesions, LeukoScan recognized 13 of the lesions as being true positive ones, 10 as being true negative ones, and 2 as being false negative ones, whereas the leukocyte scan showed 9 true positive results, 5 true negative results, and 2 false negative ones. Sensitivity specificity, and diagnostic accuracy of LeukoScan were 90.0 %, 84.6 %, and 87.9 %; and with autologous leukocyte scintigraphy were 83.9%, 76.5%, and 81.3%, respectively. The sensitivity of LeukoScan was independent of the amount of the labeled antibody injected (0.1 - < 0.5 mg, 96.2%; 0.5 - < 0.9 mg, 80.0%; 0.9 - 1.0 mg, 77.8%). False positive lesions were detected in a periprosthetic calcification, a frontal hyperostosis, and 2 periprosthetic hips that had loosened. Human antimouse antibody could not be detected in any of the 13 patients tested 1 or 3 months after injection. LeukoScan is suitable for imaging infectious lesions and may have diagnostic advantages compared with autologous leukocyte scintigraphy.

Adult↗
PubMed1996

Sonographic assessment of clubfoot deformity in young children.

We report a new diagnostic imaging technique for talipes equinovarus. Sonographic assessment of the medial border of the foot offers insight into the center of tarsal malalignment at the talonavicular joint. Technique, observations, and interpretation of the findings are delineated and compared with current radiologic evaluation of talonavicular alignment according to the method of Simons in 38 cases. The TnCE-angle is introduced as a sonographic measure to quantify talonavicular malalignment in clubfeet. Sonographic results of clubfeet are compared with those of a group of 98 normal feet. The practical implications of the method as a means for planning and control of treatment in clubfoot deformity are discussed.

Casts, Surgical↗
PubMed1996

Clinical and histologic observations of sites implanted with intraoral autologous bone grafts or allografts. 15 human case reports.

The cases reported in this paper were treated at 7 different clinical centers and present clinical and histologic observations from 15 patients and 21 human biopsies. The biopsies were taken from extraction sockets or dental implant sites which were grafted with either autologous intra-oral bone (6 sites), demineralized freeze-dried bone (DFDBA) (7 sites), or mineralized freeze-dried bone (MFDBA) (7 sites), or a combination of autologous bone, DFDBA and a barrier membrane (1 site). Six sites were grafted with DFDBA and augmented with expanded polytetrafluoroethylene (ePTFE) barrier membranes. Biopsies for histological evaluation were taken 4 to 13 months after implantation. A bone scoring system of 0 to 4 was used to evaluate the sections for dead implanted particles or the presence of vital bone. A bone score of 3 indicated the presence of dead implant material, blood vessels, islands of cartilage, osteoblasts, and new bone formation. A score of 4 indicated total replacement of the implanted material by the host bone. The average bone score for sites which received autologous bone was 2.33; for DFDBA sites, 0.98; and MFDBA was 0.18. The over-riding histologic characteristic of sites implanted with DFDBA or MFDBA was retention of non-vital graft particles within fibrous connective tissue. Biopsies taken adjacent to the host bed demonstrated incorporation of the allografts (osteoconduction). Sites grafted with autologous bone chips also demonstrated non-vital bone chips surrounded by vital host bone (osteoconduction). Sites which received barrier membranes did not appear to improve or impair bone healing of the augmented sites. Autologous bone chips harvested from within the oral cavity as well as allografts may serve as biologic fillers, but do not apparently contribute to osteoinduction. Autologous bone will eventually be resorbed and replaced by the host. DFDBA and MFDBA are resorbed very slowly and apparently do not contribute to osteoinduction. Allografts apparently are not resorbed by osteoclasts and therefore their continued use around dental implants is questioned.

Adult↗
PubMed1996

A prospective multi-center study evaluating periodontal regeneration for Class II furcation invasions and intrabony defects after treatment with a bioabsorbable barrier membrane: 1-year results.

The purpose of this prospective multi-center study was to evaluate a resorbable barrier membrane designed for periodontal regeneration. Thirty-one Class II furcations and 30 two- and three-wall intrabony defects were treated by flap debridement and bioabsorbable barrier membrane augmentation. The efficacy of treatment was evaluated in terms of changes in vertical probing depth (PD), horizontal probing depth (HPD), clinical attachment levels (CAL), and recession. Five centers participated in the study. Changes in clinical parameters are reported by individual center and by the average of the centers. All patients had either one molar with a Class II furcation or an intrabony defect. Baseline data were taken on the day of surgery. Post-treatment data were collected at 6 months and 1 year. This report is based on the 1-year findings. The average initial PD for Class II furcations was 6.1 mm. At 1 year the average PD was reduced to 3.6 mm, a 2.5 mm change. These differences were clinically and statistically significant (P < 0.0001). There was an average gain of 2.1 mm of clinical attachment (P < 0.0001) and 0.4 mm of recession (P < 0.04). There was a mean of 1.8 mm change in HPD (P < 0.0001). For intrabony defects, at 1 year there was an average PD reduction of 4.1 mm (P < 0.0001) and a mean gain of CAL of 2.9 mm (P < 0.0001). At 1 year the average recession was 0.9 mm which was statistically significant. When treatment outcomes were compared between centers there were no differences for either group of treated defects. There were differences between centers when baseline PD for furcations and intrabony sites were compared. The results of this study indicate that clinically and statistically significant improvements in PD, CAL, and HPD occurred after treatment of Class II furcations and 2- to 3-wall intrabony defects with the bioabsorbable periodontal membrane.

Adolescent↗
PubMed1996

Bifunctional NHS-BAT ester for antibody conjugation and stable technetium-99m labeling: conjugation chemistry, immunoreactivity and kit formulation.

UNLABELLED: Conjugation chemistry and kit formulated binding of the NHS ester of 6-(4'-(4"-carboxyphenoxy)butyl)-2, 10-dimercapto-2,10-dimethyl-4,8-diazaundecane (NHS-BAT ester) to monoclonal antibodies (MAbs) was investigated. The functionalities of the resulting BAT conjugated and 99mTc-labeled MAbs BW 431/26, MAb 425 and bispecific MDX210 (fragment construct) were tested by immunoreactivity and immunoscintigraphy. METHODS: The kinetics and chemistry of the conjugation reaction were monitored by high-performance liquid chromatography, size-exclusion chromatography and positive fast-atom-bombardment mass spectra (FAB-MS). The 99mTc BAT-MAbs were tested with various immunoreactivity assays. The biodistribution of 99mTc-BAT-BW 431/26 in rats was compared with directly labeled BW 431/26. RESULTS: At pH 8.5 and 25 degrees C, the reactivity of the NHS-BAT ester was high with 90% completion after 30 min. The conjugation yield of 19 microM MAb and 228 microM NHS-BAT ester amounted to 30%. Higher NHS-BAT ester concentrations afforded higher BAT-to-MAb ratios. According to FAB-MS, the conjugation competing hydrolysis surprisingly occurred at the NHS ring. Almost quantitative 99mTc labeling was achieved after 5 min at 25 degrees C. Immunoreactivity of the 99mTc-BAT antibodies showed > 90% recovery and proved to be insensitive to BAT-to-MAb ratios of up to 10. The 99mTc-BAT-BW 431/26 showed similar organ distribution but revealed less urinary excretion compared with the directly labeled BW 431/26. Immunoscintigraphy with 99mTc-labeled and BAT-BW 431/26 and BAT-MAb 425 showed the respective biological function in vivo. CONCLUSION: According to straightforward conjugation chemistry, the ease of 99mTc labeling and the application of a simple ultrafiltration technique, the NHS-BAT ester represents a nondestructive, universally applicable biofunctional ligand to introduce stable 99mTc protein binding sites. Kit formulated conjugation/labeling can be performed with little time requirements and laboratory experience.

Animals↗
PubMed1996

[Detection of antibodies against Neospora caninum in cows on Hessian farms with abortion and fertility problems].

To address the question whether N. caninum-infections occur in German cattle, 388 sera from dairy farms with abortions and fecundity problems in North Hesse were tested for antibodies to N. caninum and seropositive farms epidemiologically analyzed. 16 sera (4.1%) with titres of > or= 1:400 from a total of 10 farms (45.5% of the farms) were considered Neospora-positive. There was a conspicuous clustering of seropositive and indifferent animals in three farms. A history of abortion could not be established for all seropositive cows, a finding which may indicate that some animals mount an immune response that can protect against abortions. The validity of the indirect immunofluorescent assay for the diagnosis of the Neospora caninum-infection of cattle is discussed.

Abortion, Veterinary↗
PubMed1995

Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases.

cDNA clones of two novel Ras-related GTP-binding proteins (RagA and RagB) were isolated from rat and human cDNA libraries. Their deduced amino acid sequences comprise four of the six known conserved GTP-binding motifs (PM1, -2, -3, G1), the remaining two (G2, G3) being strikingly different from those of the Ras family, and an unusually large C-terminal domain (100 amino acids) presumably unrelated to GTP binding. RagA and RagB differ by seven conservative amino acid substitutions (98% identity), and by 33 additional residues at the N terminus of RagB. In addition, two isoforms of RagB (RagBs and RagB1) were found that differed only by an insertion of 28 codons between the GTP-binding motifs PM2 and PM3, apparently generated by alternative mRNA splicing. Polymerase chain reaction amplification with specific primers indicated that both long and short form of RagB transcripts were present in adrenal gland, thymus, spleen, and kidney, whereas in brain, only the long form RagB1 was detected. A long splicing variant of RagA was not detected. Recombinant glutathione S-transferase (GST) fusion proteins of RagA and RagBs bound large amounts of radiolabeled GTP gamma S in a specific and saturable manner. In contrast, GTP gamma S binding of GST-RagB1 hardly exceeded that of recombinant GST. GTP gamma S bound to recombinant RagA, and RagBs was rapidly exchangeable for GTP, whereas no intrinsic GTPase activity was detected. A multiple sequence alignment indicated that RagA and RagB cannot be assigned to any of the known subfamilies of Ras-related GTPases but exhibit a 52% identity with a yeast protein (Gtr1) presumably involved in phosphate transport and/or cell growth. It is suggested that RagA and RagB are the mammalian homologues of Gtr1 and that they represent a novel subfamily of Ras-homologous GTP binding proteins.

Amino Acid Sequence↗
PubMed1995

Targeting of liver metastases of colorectal cancer with IgG, F(ab')2, and Fab' anti-carcinoembryonic antigen antibodies labeled with 99mTc: the role of metabolism and kinetics.

The aim of this study was to investigate targeting of the liver metastases by directly 99mTc-labeled complete (IgG) and fragmented antibodies [F(ab')2 and Fab'] in relation to their kinetics and metabolic fate. A total of 127 patients with metastatic colorectal cancer were examined [IgG1, BW 431/26 (Behringwerke, Marburg, Germany) n = 50; F(ab')2, F023C5 (Sorin Biomedica, Saluggia, Italy) n = 58; Fab', IMMU-4 (Immunomedics, Morris Plains, NJ) n = 19]. Native monoclonal antibodies (MAbs), serum samples from 10 min to 24 h postinjection (p.i.), and urine were analyzed by gel filtration chromatography. Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 min to 24 h p.i. (region-of-interest technique). In BW 431/26, 96% of injected activity was labeled IgG1; in F023C5, 29% was F(ab')2, and 71% was Fab'; and in IMMU-4, 92% was Fab', and 8% was F(ab')2. Serum half-lives were: IgG1, 36 h (liver uptake predominant); F(ab')2, 16 h; and Fab', 4 h (renal uptake predominant). All MAbs were metabolized, fragments more rapidly than IgG, to low-molecular-weight products and excreted into the urine (e.g., Tc-cystine). In targeting liver metastases, sensitivities were found to be higher for fragments (44.1, 72.5, and 80% for BW 431/26, F023C5, and IMMU-4, respectively) but at significantly lower tumor:background ratios than with IgG (1.78 +/- 0.29 versus 1.29 +/- 0.11 and 1.43 +/- 0.53; P < 0.01). With IgG, there was a continuous tumor uptake over 24 h, whereas with fragments, the maximal uptake occurred mostly within 1 h, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4 h with fragments but often not before 24 h with IgG. These results show that the higher sensitivity of fragments in liver lesion targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact MAbs show a slow, continuous uptake, leading to higher tumor:background ratios at later p.i. times, often beyond the imaging possibilities of 99mTc.

Carcinoembryonic Antigen↗
PubMed1995

Mutation of two conserved arginine residues in the glucose transporter GLUT4 supresses transport activity, but not glucose-inhibitable binding of inhibitory ligands.

Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK-) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.

Animals↗
PubMed1995

The contribution of nuclear medicine to the patient with infection.

Nuclear medicine imaging of infection has two major indications: (a) the localization of a focus of infection in patients with fever of unknown origin; in this context the radio-pharmaceutical should be highly sensitive whereas specificity is not so important because subsequent biopsy or morphologically based imaging can be performed; (b) the diagnosis of an infection in patients with localized symptoms, for example after surgery, when normal anatomy is absent or when metal implants prevent computed tomography or magnetic resonance imaging. In these latter cases high sensitivity and to an even greater extent high specificity are mandatory to guide further clinical management (conservative or surgical). All radiopharmaceuticals available to date, such as technetium-99m nanocolloids, gallium-67 citrate, indium-111- and 99mTc-labelled white blood cells, 99mTc-antigranulocyte antibodies, and 99mTc-or 111In-labelled unspecific human immunoglobulin, have different biodistributions and different physical characteristics. The absence of physiological uptake in an organ and the radiation exposure of a patient are reasons to use different radiopharmaceuticals in different clinical situations, adapted to the individual circumstances of the patient.

Citrates↗